title: Fumonisin B1 inhibits mitochondrial respiration and deregulates calcium homeostasis--implication to mechanism of cell toxicity.
abstract: Fumonisin B(1) (FB(1)) is a neurodegenerative mycotoxin produced by Fusarium verticiloides mould that contaminates maize worldwide. FB(1) toxicity has been connected with deregulation of sphingolipid metabolism, but the mechanism of cytotoxicity remains controversial. In cell cultures of rat primary astrocytes and human neuroblastoma (SH-SY5Y), we found that FB(1) inhibits mitochondrial complex I, which leads to a decrease in the rate of mitochondrial and cellular respiration, depolarisation of the mitochondrial membrane, induction of reactive oxygen species (ROS) production in mitochondria and deregulation of calcium signalling. Despite the increase in ROS production, the intracellular level of glutathione (GSH) was significantly increased. After 24h of FB(1) exposure, no cell death was observed. Thus, mitochondria appear to be the primary target of FB(1), which leads to sustained deregulation of calcium homeostasis and presumably to cell death.
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Ana-Marija
authors.initials: AM
authors.lastname: Domijan
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Abramov
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D042967:Electron Transport Complex I / Q000378:metabolism; D037341:Fumonisins / Q000494:pharmacology*; D005670:Fusarium; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D037341:Fumonisins; D017382:Reactive Oxygen Species; C056933:fumonisin B1; D042967:Electron Transport Complex I; D005978:Glutathione